GH antagonizes the action of insulin at the postreceptor level in skeletal muscle and adipose tissue (but not the liver). Hypophysectomy (removal of the pituitary gland) can improve diabetic management because GH, like cortisol, decreases insulin sensitivity. Because GH produces insulin insensitivity, it is considered a diabetogenic hormone. Therefore when secreted in excess (e.g., in acromegaly), GH can cause diabetes mellitus, and the insulin levels necessary to maintain normal metabolism increase. Excessive insulin secretion resulting from an excess of GH can cause damage to pancreatic beta cells. In the absence of GH, insulin secretion declines. Thus normal levels of GH are required for normal pancreatic function and insulin secretion.
GH deficiency in adults is becoming recognized as a pathological syndrome. If GH deficiency occurs after the epiphyses close, growth is not impaired. GH deficiency is one of many possible causes of hypoglycemia. Recent studies have shown that extended deficiencies of GH lead to changes in body composition. Fat as a percentage of body weight increases, whereas lean body mass declines. In addition, muscle weakness and early exhaustion are symptoms of GH deficiency. There has been interest in using GH in elderly populations to reverse age-related physical decline and body composition, but studies to date have shown small changes in body composition, no functional benefits, and increased risk of adverse events.
GHisnecessaryforgrowthbeforeadulthood.GHdeficienciesresultinseveregrowthdeficits,andexcessesresultingigantism.ExcessGHinadulthoodafterepiphysealclosurecausesacromegaly, characterizedbyinsidiousenlargementofthehandsandfeet,coarseningoffacialfeatures,insulinresistance,anddiabetes.GeneticdisordersoftheGH–IGF-Iaxiscauseseveregrowthimpairment.IdentifiedmutationscausingisolatedGHdeficiencymostcommonlyoccurintheGHandGHRHreceptorgenes.ThesepatientscanbetreatedwithrecombinanthGHtorestorefunctionofthedownstreamaxis.InLaronsyndrome,amutationoftheGHreceptorcausesGHresistance.InthisinstancetheliverdoesnotproduceIGF-I;thisisduetoalackofresponsivenesstoGH.ThesepatientscanbetreatedwithIGF-I,butwithoutthedirectactionsofGH,theeffectivenessofthetreatmentislimited.OtherdownstreamgeneticmutationsthathavebeenreportedincludethoseinSTAT5B,IGF-I,andALS.
The Lactotrope
The lactotrope produces the hormone prolactin, which is a 199–amino acid single-chain protein. PRL is structurally related to GH and hPL (see ). Like GH, the PRL receptor is a member of the cytokine family coupled to the JAK/STAT signaling pathways. Because the primary action of PRL in humans is related to breast development and function during pregnancy and lactation, the regulation and actions of prolactin will be discussed in detail in
In the context of the pituitary gland, it should be appreciated that the lactotrope differs from the other endocrine cell types of the adenohypophysis in two major ways: 1.
The lactotrope is not part of an endocrine axis. This means PRL acts directly on nonendocrine cells (primarily of the breast) to induce physiological changes.
2.